This application addresses broad Challenge Area (01) Behavior, Behavioral Change, and Prevention and specific Challenge Topic, 01-AG-102: Neural mechanisms of behavioral change. Cognitive decline in normal aging is a very important societal problem, which impacts millions of people worldwide. Specifically, normal aging is accompanied by declines in working memory and executive function/attention control, as well as in long term memory and speed of processing. Thus, increasing knowledge about the possible predictors of age- related cognitive impairments and their interactions can yield substantial societal and economic benefits, by providing means of early detection and thus improving the chances of successful prevention and/or treatment. Recent studies have emphasized that physical activity and fitness may help stave off some of the effect of aging on cognition, and specifically those related to working memory and executive function, although the exact mechanisms through which these gains are obtained are not yet completely understood. In this work we will conduct a detailed investigation of the possible mediating role that the health status of the cerebrovascular system may have on the beneficial effects of physical fitness on brain anatomy and function and cognitive performance. Our approach is based on the assumption that all the phenomena under study (physical fitness/activity, cerebrovascular health, brain anatomy and function, and cognitive function) are in fact complex and multifaceted and best studied using a multivariate approach. Therefore, for each of them, we take multiple measures at multiple levels. We will investigate naturally-occurring variability in a sample of normally-aging adults comprising four age groups (50-60, 60-70, 70-80, and 80-90 years old), which will be measured twice at 12 months distance (thus affording both cross-sectional and short-term longitudinal analyses). A multimodal imaging approach based on a combination of magnetic resonance imaging, diffusive near-infrared spectroscopic imaging, and electrophysiological methods will be used to provide maps of both cerebrovascular status and brain anatomy and function. Societal Impact. Cognitive decline in aging affects millions of people worldwide. Its early detection may lead to prevention and improvement in intervention practices, thus providing incalculable benefits to society both in economic and humanitarian terms. Physical activity regimes have shown to be beneficial to cognitive aging. Therefore, a better understanding of the mechanisms through which these benefits are accrued is of enormous practical significance. In addition, following the guidelines of ARRA 2009 for these Challenge proposals, we underscore the fact that this proposal, if funded, will generate one new position (graduate research assistant) and allow for the retention of two additional positions (senior research scientist and research specialist) who may otherwise lose employment. It is further expected that, through this funding, these investigators will receive valuable training in the biomedical sciences, which will make them more competitive on job market in the future. PUBLIC HEALTH RELEVANCE: Cognitive decline in aging affects millions of people worldwide. Its early detection may lead to prevention and improvement in intervention practices, thus providing incalculable benefits to society both in economic and humanitarian terms. Physical activity regimes have shown to be beneficial to cognitive aging. Therefore, a better understanding of the mechanisms through which these benefits are accrued is of enormous practical significance. In addition, following the guidelines of ARRA 2009 for these Challenge proposals, we underscore the fact that this proposal, if funded, will generate one new position (graduate research assistant) and allow for the retention of two additional positions (senior research scientist and research specialist) who may otherwise lose employment. It is further expected that, through this funding, these investigators will receive valuable training in the biomedical sciences, which will make them more competitive on job market in the future.